Impaired Estrogen Sensitivity in Bone by Inhibiting Both Estrogen Receptor α and β Pathways

Although it is well established that estrogen deficiency causes osteoporosis among the postmenopausal women, the involvement of estrogen receptor (ER) in its pathogenesis still remains uncertain. In the present study, we have generated rats harboring a dominant negative ERα, which inhibits the actio...

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Published in:The Journal of biological chemistry 2000-07, Vol.275 (28), p.21372-21379
Main Authors: Ogawa, Sumito, Fujita, Masayo, Ishii, Yasunori, Tsurukami, Hiroshi, Hirabayashi, Masami, Ikeda, Kazuhiro, Orimo, Akira, Hosoi, Takayuki, Ueda, Masatsugu, Nakamura, Toshitaka, Ouchi, Yasuyoshi, Muramatsu, Masami, Inoue, Satoshi
Format: Article
Language:English
Subjects:
Animals
Animals, Genetically Modified
Bone Density - drug effects
Bone Density - genetics
Bone Density - physiology
Chickens
Estradiol - pharmacology
Estrogen Receptor alpha
Estrogen Receptor beta
Female
Humans
Male
Osteoporosis - etiology
Ovariectomy
Rats
Rats, Wistar
Receptors, Estrogen - genetics
Receptors, Estrogen - physiology
Reverse Transcriptase Polymerase Chain Reaction
Transcription, Genetic
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Summary:Although it is well established that estrogen deficiency causes osteoporosis among the postmenopausal women, the involvement of estrogen receptor (ER) in its pathogenesis still remains uncertain. In the present study, we have generated rats harboring a dominant negative ERα, which inhibits the actions of not only ERα but also recently identified ERβ. Contrary to our expectation, the bone mineral density (BMD) of the resulting transgenic female rats was maintained at the same level with that of the wild-type littermates when sham-operated. In addition, ovariectomy-induced bone loss was observed almost equally in both groups. Strikingly, however, the BMD of the transgenic female rats, after ovariectomized, remained decreased even if 17β-estradiol (E2) was administrated, whereas, in contrast, the decrease of littermate BMD was completely prevented by E2. Moreover, bone histomorphometrical analysis of ovariectomized transgenic rats revealed that the higher rates of bone turnover still remained after treatment with E2. These results demonstrate that the prevention from the ovariectomy-induced bone loss by estrogen is mediated by ER pathways and that the maintenance of BMD before ovariectomy might be compensated by other mechanisms distinct from ERα and ERβ pathways.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M909675199